PTPN21 Overexpression Promotes Osteogenic and Adipogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells but Inhibits the Immunosuppressive Function

Protein tyrosine phosphatases (PTPs) act as key regulators in various cellular processes such as proliferation, differentiation, and migration. Our previous research demonstrated that non-receptor-typed PTP21 (PTPN21), a member of the PTP family, played a critical role in the proliferation, cell cyc...

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Main Authors: Huafang Wang, Xiaohang Ye, Haowen Xiao, Ni Zhu, Cong Wei, Xiang Sun, Limengmeng Wang, Binsheng Wang, Xiaohong Yu, Xiaoyu Lai, Shan Fu, He Huang
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2019/4686132
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author Huafang Wang
Xiaohang Ye
Haowen Xiao
Ni Zhu
Cong Wei
Xiang Sun
Limengmeng Wang
Binsheng Wang
Xiaohong Yu
Xiaoyu Lai
Shan Fu
He Huang
author_facet Huafang Wang
Xiaohang Ye
Haowen Xiao
Ni Zhu
Cong Wei
Xiang Sun
Limengmeng Wang
Binsheng Wang
Xiaohong Yu
Xiaoyu Lai
Shan Fu
He Huang
author_sort Huafang Wang
collection DOAJ
description Protein tyrosine phosphatases (PTPs) act as key regulators in various cellular processes such as proliferation, differentiation, and migration. Our previous research demonstrated that non-receptor-typed PTP21 (PTPN21), a member of the PTP family, played a critical role in the proliferation, cell cycle, and chemosensitivity of acute lymphoblastic leukemia cells. However, the role of PTPN21 in the bone marrow microenvironment has not yet been elucidated. In the study, we explored the effects of PTPN21 on human bone marrow-derived mesenchymal stem cells (BM-MSCs) via lentiviral-mediated overexpression and knock-down of PTPN21 in vitro. Overexpressing PTPN21 in BM-MSCs inhibited the proliferation through arresting cell cycle at the G0 phase but rendered them a higher osteogenic and adipogenic differentiation potential. In addition, overexpressing PTPN21 in BM-MSCs increased their senescence levels through upregulation of P21 and P53 and dramatically changed the levels of crosstalk with their typical target cells including immunocytes, tumor cells, and vascular endothelial cells. BM-MSCs overexpressing PTPN21 had an impaired immunosuppressive function and an increased capacity of recruiting tumor cells and vascular endothelial cells in a chemotaxis transwell coculture system. Collectively, our data suggested that PTPN21 acted as a pleiotropic factor in modulating the function of human BM-MSCs.
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spelling doaj-art-3b3e7f3a4e664b96b291eed31d8e6cba2025-08-20T03:55:36ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/46861324686132PTPN21 Overexpression Promotes Osteogenic and Adipogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells but Inhibits the Immunosuppressive FunctionHuafang Wang0Xiaohang Ye1Haowen Xiao2Ni Zhu3Cong Wei4Xiang Sun5Limengmeng Wang6Binsheng Wang7Xiaohong Yu8Xiaoyu Lai9Shan Fu10He Huang11Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, ChinaBone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, ChinaDepartment of Hematology, The Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310000, ChinaDepartment of Hematology, The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou 310000, ChinaBone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, ChinaZhejiang University-University of Edinburgh Institute, International Campus Zhejiang University, Haining 314400, ChinaBone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, ChinaBone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, ChinaZhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou 310000, ChinaBone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, ChinaBone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, ChinaBone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, ChinaProtein tyrosine phosphatases (PTPs) act as key regulators in various cellular processes such as proliferation, differentiation, and migration. Our previous research demonstrated that non-receptor-typed PTP21 (PTPN21), a member of the PTP family, played a critical role in the proliferation, cell cycle, and chemosensitivity of acute lymphoblastic leukemia cells. However, the role of PTPN21 in the bone marrow microenvironment has not yet been elucidated. In the study, we explored the effects of PTPN21 on human bone marrow-derived mesenchymal stem cells (BM-MSCs) via lentiviral-mediated overexpression and knock-down of PTPN21 in vitro. Overexpressing PTPN21 in BM-MSCs inhibited the proliferation through arresting cell cycle at the G0 phase but rendered them a higher osteogenic and adipogenic differentiation potential. In addition, overexpressing PTPN21 in BM-MSCs increased their senescence levels through upregulation of P21 and P53 and dramatically changed the levels of crosstalk with their typical target cells including immunocytes, tumor cells, and vascular endothelial cells. BM-MSCs overexpressing PTPN21 had an impaired immunosuppressive function and an increased capacity of recruiting tumor cells and vascular endothelial cells in a chemotaxis transwell coculture system. Collectively, our data suggested that PTPN21 acted as a pleiotropic factor in modulating the function of human BM-MSCs.http://dx.doi.org/10.1155/2019/4686132
spellingShingle Huafang Wang
Xiaohang Ye
Haowen Xiao
Ni Zhu
Cong Wei
Xiang Sun
Limengmeng Wang
Binsheng Wang
Xiaohong Yu
Xiaoyu Lai
Shan Fu
He Huang
PTPN21 Overexpression Promotes Osteogenic and Adipogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells but Inhibits the Immunosuppressive Function
Stem Cells International
title PTPN21 Overexpression Promotes Osteogenic and Adipogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells but Inhibits the Immunosuppressive Function
title_full PTPN21 Overexpression Promotes Osteogenic and Adipogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells but Inhibits the Immunosuppressive Function
title_fullStr PTPN21 Overexpression Promotes Osteogenic and Adipogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells but Inhibits the Immunosuppressive Function
title_full_unstemmed PTPN21 Overexpression Promotes Osteogenic and Adipogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells but Inhibits the Immunosuppressive Function
title_short PTPN21 Overexpression Promotes Osteogenic and Adipogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells but Inhibits the Immunosuppressive Function
title_sort ptpn21 overexpression promotes osteogenic and adipogenic differentiation of bone marrow derived mesenchymal stem cells but inhibits the immunosuppressive function
url http://dx.doi.org/10.1155/2019/4686132
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